The Nobel Prize in Physiology or Medicine 2007
Mario R. Capecchi, Sir Martin J. Evans, Oliver Smithies
Telephone interview with Professor Mario R. Capecchi immediately following the announcement of the 2007 Nobel Prize in Physiology or Medicine, October 8, 2007. The interviewer is Adam Smith, Editor-in-Chief of Nobelprize.org.
[Unknown] – Hello.
[Adam Smith] – Hello, my name's Adam Smith, may I speak to Mario Capecchi please.
[Unknown] – Yes, just a minute please.
[AS] – Thank you.
[Mario Capecchi] – Hello.
[AS] – Hello, my name is Adam Smith and I'm calling from the Nobel Foundation's official website, Nobelprize.org. We have a tradition of recording very brief interviews with new Laureates, so would it be alright if I asked you a few questions.
[MC] – Sure, please.
[AS] – Thank you. First of all, very many congratulations on the award.
[MC] – Thank you very much.
[AS] – I imagine that, it being early, the call may have come while you were still asleep.
[MC] – Sound asleep.
[AS] – And were you able to gather your thoughts, and have some reaction to the call?
[MC] – No, it's a marvellous call, and it's a wonderful surprise. And also I'm very happy that my colleagues Martin Evans and Oliver Smithies both, are also receiving the Nobel Prize.
[AS] – Yes, the three of you have been united in several prizes now, and …
[MC] – Yeah, we're good friends and it's been, there's a small amount of competition but also mostly good friendship all the way along the way.
[AS] – That's nice. Yours might be considered a particularly inspiring path to the Nobel Prize since, am I right in saying that you didn't go to school until you were nine years old, having been a child wandering in war-time Italy?
[MC] – That's correct.
[AS] – And is it right, am I right in saying that you didn't read and write until you were 9?
[MC] – That's correct.
[AS] – So what did that experience teach you? Is it possible to summarize?
[MC] – Well I think what it provided was resourcefulness, and I think just the drive to keep yourself, maintain yourself, and survive. I think it led me to be able to use my own resources, to be able to get through life. And I think now I'm also very grateful, in a sense it's fantastic. I mean most children didn't make it, I think I was extremely lucky.
[AS] – Does it also say something about the potential of young people, that they …?
[MC] – Oh, certainly, no, that's the one thing that I think is extremely important, is that anyone can do it, if given a chance, if given the opportunity.
[AS] – Shortly after graduating from University you found yourself studying with Jim Watson ...
[MC] – That's correct.
[AS] – … of DNA fame. What did you learn from him?
[MC] – He was a fantastic mentor, I consider him … essentially he helped me enormously with science and I used him as an example. It was a marvellous opportunity to be in his laboratory and also actually Wally Gilbert was in the same laboratory at the same time. So there were actually two people that received the Nobel Prize. So I consider myself a second generation.
[AS] – Presumably they taught you resilience as well because in your initial experiments, where you were attempting to prove that it was possible to use homologous recombination to produce specific gene targeting in cultured cells, there was some resistance to that idea. And I believe it was somewhat hard to obtain funding to do that research.
[MC] – That's correct. No, our first grant was actually refused with respect to that project, mainly because they didn't think it was possible. The probability that an exogenous piece of DNA would be able to find the cognate sequence in three-thirty base pairs was thought to be not a significant possibility. So I think that was the resistance, and I think we just had the feeling that if we could make the assay sensitive enough, we knew it was going to be a rare event, but if we could make the assay sensitive enough then we knew we might be able to detect it. And the other thing to keep in mind is that this is actually before the yeast system was working, so we had no precedent. We did know that it could happen in bacteria.
[AS] – Then you happened upon Martin Evans, whose embryonic stem cells provided the vehicle for transmitting these genetic alterations into the germline of mice.
[MC] – Right.
[AS] – How did that meeting come about?
[MC] – Well, I'd heard about the results at a Gordon conference the previous summer and so I actually called him and my wife and I went there, and spent actually a couple of weeks in Christmas, right before Christmas, to learn about ES cells. So that was extremely important for us to do that and get first hand experience in how to grow them, how to manipulate them, and also how to inject them into pre-implantation embryos so that I'd be able to use them to generate mice. So we actually got direct instructions from the people that actually worked them out. That included Martin and also Liz Robertson.
[AS] – Between you, the work you did then and the discoveries you made then has led to the development of many thousands of knock-out and knock-in mice. What's your hope for what this technology can deliver in the future?
[MC] – I think what it will do in the future is that there now are better and better techniques for manipulating the genome in more and more sophisticated ways, both using conditional mutagenesis, also using much more sophisticated reporters. And my guess is also, it will become multiplex, so that you will not only be working with a few genes but many genes at the same time. You will be able to manipulate their expression, and place of expression as well as time of expression, and probably also modulate how much gene product is being made. So I think, my own feeling is that even though, to me it was always a gamble, you know, how complicated is a mouse and is it actually penetrable by this kind of technology and then at the same time can we make the technology sophisticated enough to be able to handle essentially very complex questions. Eventually what we would like to do is be able to extend it to studying other mammalian organisms so we aren't simply restricted with respect to finding out how does a mouse work, and its analogy to humans, but also be able to utilize it to study more processes in evolution and how different traits have come up during evolution. So those are the kind of questions we're looking forward to in the future.
[AS] – Thank you very much indeed. Well, we interview Laureates again when they come to receive their Nobel Prizes in Stockholm in December, so hopefully we'll have a chance to speak again then.
[MC] – Thanks.
[AS] – Thank you very much indeed. Bye, bye.
[MC] – Thank you, bye, bye.
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